Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis
<br><strong>Objective: </strong>To investigate whether lipid-related or body mass index (BMI)–related common genetic polymorphisms modulate the associations between serum lipid levels, BMI and disability progression in multiple sclerosis (MS).</br> <br><strong>Me...
| প্রধান লেখক: | , , , , , , , , , , |
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| অন্যান্য লেখক: | |
| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
BMJ Publishing Group
2019
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| _version_ | 1826282008842600448 |
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| author | Zhang, Y Zhou, Y van der Mei, IAF Simpson, S Ponsonby, A-L Lucas, RM Tettey, P Charlesworth, J Kostner, K Taylor, BV Ausimmune/AusLong Investigators Group |
| author2 | Dwyer, T |
| author_facet | Dwyer, T Zhang, Y Zhou, Y van der Mei, IAF Simpson, S Ponsonby, A-L Lucas, RM Tettey, P Charlesworth, J Kostner, K Taylor, BV Ausimmune/AusLong Investigators Group |
| author_sort | Zhang, Y |
| collection | OXFORD |
| description | <br><strong>Objective: </strong>To investigate whether lipid-related or body mass index (BMI)–related common genetic polymorphisms modulate the associations between serum lipid levels, BMI and disability progression in multiple sclerosis (MS).</br>
<br><strong>Methods: </strong>The association between disability progression (annualised Expanded Disability Status Scale (EDSS) change over 5 years, ΔEDSS) and lipid-related or BMI-related genetic polymorphisms was evaluated in a longitudinal cohort (n=184), diagnosed with MS. We constructed a cumulative genetic risk score (CGRS) of associated polymorphisms (p<0.05) and examined the interactions between the CGRS and lipid levels (measured at baseline) in predicting ΔEDSS. All analyses were conducted using linear regression.</br>
<br><strong>Results: </strong>Five lipid polymorphisms (rs2013208, rs9488822, rs17173637, rs10401969 and rs2277862) and one BMI polymorphism (rs2033529) were nominally associated with ΔEDSS. The constructed lipid CGRS showed a significant, dose-dependent association with ΔEDSS (ptrend=1.4×10−6), such that participants having ≥6 risk alleles progressed 0.38 EDSS points per year faster compared with those having ≤3. This CGRS model explained 16% of the variance in ΔEDSS. We also found significant interactions between the CGRS and lipid levels in modulating ΔEDSS, including high-density lipoprotein (HDL; pinteraction=0.005) and total cholesterol:high-density lipoprotein ratio (TC:HDL; pinteraction=0.030). The combined model (combination of CGRS and the lipid parameter) explained 26% of the disability variance for HDL and 27% for TC:HDL.</br>
<br><strong>Interpretation: </strong>In this prospective cohort study, both lipid levels and lipid-related polymorphisms individually and jointly were associated with significantly increased disability progression in MS. These results indicate that these polymorphisms and tagged genes might be potential points of intervention to moderate disability progression.</br> |
| first_indexed | 2024-03-07T00:37:24Z |
| format | Journal article |
| id | oxford-uuid:81e4d940-821a-4448-8668-8f6d55026d40 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:37:24Z |
| publishDate | 2019 |
| publisher | BMJ Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:81e4d940-821a-4448-8668-8f6d55026d402022-03-26T21:33:26ZLipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:81e4d940-821a-4448-8668-8f6d55026d40EnglishSymplectic ElementsBMJ Publishing Group2019Zhang, YZhou, Yvan der Mei, IAFSimpson, SPonsonby, A-LLucas, RMTettey, PCharlesworth, JKostner, KTaylor, BVAusimmune/AusLong Investigators GroupDwyer, T<br><strong>Objective: </strong>To investigate whether lipid-related or body mass index (BMI)–related common genetic polymorphisms modulate the associations between serum lipid levels, BMI and disability progression in multiple sclerosis (MS).</br> <br><strong>Methods: </strong>The association between disability progression (annualised Expanded Disability Status Scale (EDSS) change over 5 years, ΔEDSS) and lipid-related or BMI-related genetic polymorphisms was evaluated in a longitudinal cohort (n=184), diagnosed with MS. We constructed a cumulative genetic risk score (CGRS) of associated polymorphisms (p<0.05) and examined the interactions between the CGRS and lipid levels (measured at baseline) in predicting ΔEDSS. All analyses were conducted using linear regression.</br> <br><strong>Results: </strong>Five lipid polymorphisms (rs2013208, rs9488822, rs17173637, rs10401969 and rs2277862) and one BMI polymorphism (rs2033529) were nominally associated with ΔEDSS. The constructed lipid CGRS showed a significant, dose-dependent association with ΔEDSS (ptrend=1.4×10−6), such that participants having ≥6 risk alleles progressed 0.38 EDSS points per year faster compared with those having ≤3. This CGRS model explained 16% of the variance in ΔEDSS. We also found significant interactions between the CGRS and lipid levels in modulating ΔEDSS, including high-density lipoprotein (HDL; pinteraction=0.005) and total cholesterol:high-density lipoprotein ratio (TC:HDL; pinteraction=0.030). The combined model (combination of CGRS and the lipid parameter) explained 26% of the disability variance for HDL and 27% for TC:HDL.</br> <br><strong>Interpretation: </strong>In this prospective cohort study, both lipid levels and lipid-related polymorphisms individually and jointly were associated with significantly increased disability progression in MS. These results indicate that these polymorphisms and tagged genes might be potential points of intervention to moderate disability progression.</br> |
| spellingShingle | Zhang, Y Zhou, Y van der Mei, IAF Simpson, S Ponsonby, A-L Lucas, RM Tettey, P Charlesworth, J Kostner, K Taylor, BV Ausimmune/AusLong Investigators Group Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis |
| title | Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis |
| title_full | Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis |
| title_fullStr | Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis |
| title_full_unstemmed | Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis |
| title_short | Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis |
| title_sort | lipid related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis |
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